This proposal is the first competitive renewal of the Mental Health Clinical Research Center (MHCRC) since 1988, when there was a change in Center leadership. The Center has now focused its efforts on further characterizing the brain dysmorphology of schizophrenia and understanding its functional significance. To broaden this characterization we will study other psychiatric and neurological patient groups, sharing putative behavioral or structural abnormalities with schizophrenic patients. Comparison disorders include complex partial epilepsy, psychotic depression and schizophrenia with comorbid alcoholism. Schizophrenia is conceived of as a brain disease, with its genesis a pathological event probably occurring some considerable time before the clinical onset of the disorder. The clinical manifestations of the disease are the result of pathological brain processes, of which the observable brain dysmorphology is a marker. In addition, dysfunction in motor, cognitive, and electrophysiological processes are probably related to the brain dysmorphology. The temporal course of the pathological processes, as well as factors such as aging, gender age of symptom onset and duration of illness since clinical onset, may influence the brain dysmorphology and contribute to the clinical, behavioral and biological heterogeneity of schizophrenia. The MHCRC consists of Administrative, Clinical and Biostatistical/Database Cores, plus five Scientific Cores (Structural Neuroimaging, Functional Neuroimaging, Experimental Neuropsychology, Waking Electrophysiology and Sleep Electrophysiology). Some studies performed by Core laboratories are designed to test whether the brain dysmoprphology and dysfunction are localized and focal or are widely distributed. Other studies are theoretically independent of questions about brain structure. New functional imaging studies will complement the structural studies and include positron emission tomography, magnetic resonance spectroscopic imaging, and functional magnetic resonance imaging. The Center has an inpatient diagnosis and treatment facility and an outpatient follow-up program. We have established a collaboration with a large stat hospital allowing us to study patients with more severe disease and earlier onset, and we have established collaborations with specialty clinics at Stanford University Medical Center for recruitment of patients with comparison diagnoses. The MHCRC also serves as a training site for medical students, residents and fellows.